Thyrotropin (TSH) is the primary regulator of thyroid function and it is important to determine factors that control its regulation and action. Heterogeneous forms of TSH differing in carbohydrate structure display different actions in different assay systems. Enzymatic deglycosylation causes inhibition of TSH activity in most bioassays, primarily at a post-receptor step. Thus, carbohydrate modulates the action of TSH in a qualitative manner, in addition to the primary transcriptional control of TSH synthesis which regulates the quality of the hormone. Certain human diseases such as thyroid hormone resistance cause abnormal regulation of TSH as well as decreased growth in children. We are currently treating such patients with large doses of thyroid hormone in an attempt to correct both the pituitary and growth defect.